Psoriasis is a chronic skin disease characterized by keratinocyte hyperproliferation and altered differentiation which affects 1-2% of the American population. Research aimed at the pathogenesis of psoriasis has increasingly been directed at the role of immune system and cell surface membrane alterations (structural and biochemical--including alterations in glycoproteins and growth receptors). To integrate these two perspectives, we propose to dissect and characterize a specific lymphocyte-keratinocyte reaction at the molecular biochemical cell surface level. This will be accomplished by utilizing gamma interferon (which is produced by activated lymphocytes) and cultured keratinocytes obtained from normal and psoriatic patients. We have focused on gamma interferon because it influences keratinocyte growth and protein synthesis, both of which are altered in psoriasis. Our hypothesis is that an altered lymphocyte-keratinocyte association and specific keratinocyte membrane alterations are of fundamental importance in the pathogenesis of psoriasis. By studying the iodinated recombinant gamma interferon binding to normal and psoriatic keratinocytes as well as the effects of exposure to other growth modulators; epidermal growth factor, cholera toxin, insulin, platelet derived growth factor and interleukin-1; various proteases (neutrophilic, plasminogen activator, etc.); and treatment modalities (glucocorticosteroids, ultraviolet light, anthralin) on ligand binding, we hope to gain insight into specific biochemical differences which may be responsible for psoriasis. We also plan to study the role of immune system in wound healing as a model in which there is controlled keratinocyte proliferation to clarify possible immunological aberrations which may contribute to the uncontrolled keratinocyte proliferation seen in psoriasis. Since T lymphocytes are the initial inflammatory cells in psoriasis and keratinocytes in vitro respond to gamma interferon at 10-11M by decreasing proliferation and synthesizing new proteins, including HLA-DR, the lack of HLA-DR posotivity and hyperproliferation seen in psoriasis may reflect an inadequate amount of gamma interferon or an altered response of the keratinocytes to this lymphokine. More detailed studies involving lymphocyte-keratinocyte interaction may provide the rational basis for the development of new, improved treatment modalities for psoriasis.